ObjectiveTo explore the feasibility of constructing a programmed death receptor-1（PD-1） molecular probe for non-invasive micro-positron emission tomography/computed tomography （Micro-PET/CT） imaging of PD-1 protein in mouse S180 sarcoma. MethodsA transgenic PD-1 C57 S180 sarcoma mouse model was established using the S180 sarcoma cell injection. Furthermore， ¹²⁴I-anti-PD-1 monoclonal antibody probe was synthesized. 18.5 MBq of the ¹²⁴I-anti-PD-1 probe was injected into the tail vein of transgenic PD-1 C57 mice. Subsequently， S180 sarcoma was imaged using Micro-PET/CT. ResultsStudy successfully established a transgenic PD-1 C57 S180 sarcoma mouse model. Immunohistochemical （IHC） results showed PD-1 protein expression in S180 sarcoma. Micro-PET/CT imaging successfully visualized the PD-1 protein receptor in S180 sarcoma at different time points （20， 48， 72， and 120 h） after probe injection. ConclusionThe ¹²⁴I-anti-PD-1 monoclonal antibody molecular probe successfully targets the PD-1 receptor in S180 sarcoma of transgenic PD-1 C57 mice， and presents clear Micro-PET/CT immunoassay results， thus it potentially enables the non-invasive screening of patients with PD-1 positive malignant tumors.

Transcatheter aortic valve replacement (TAVR) has emerged as the first-line treatment for aortic valve stenosis. Coronary obstruction is a severe complication of TAVR, with mortality rates exceeding 30%. Coronary obstruction can be classified as acute or delayed based on the timing of the onset, and as direct or indirect obstruction according to the underlying mechanism. Risk factors for predicting coronary obstruction include a small sinus of Valsalva diameter, excessively long native leaflets, low coronary height, and small sinotubular junction height and diameter. Accurate preoperative assessment of these anatomical parameters using CT is crucial for selecting the appropriate valve type, size, and implantation depth. Preventive technical strategies for coronary obstruction include intraoperative interventional treatments (such as the "Chimney" stenting technique), leaflet modification (such as the BASILICA technique), and alignment of the annulus and coronaries. These techniques have demonstrated significant efficacy in reducing the incidence of coronary obstruction and associated mortality. This paper reviews the epidemiology, classification, and mechanisms of coronary obstruction, with a particular focus on the identification, prevention, and treatment of high-risk patients. The aim is to highlight the importance of recognizing and managing coronary risks during TAVR and to provide actionable recommendations for the prevention and treatment of coronary obstruction in clinical practice.
Humans ; Transcatheter Aortic Valve Replacement/methods* ; Risk Factors ; Aortic Valve Stenosis/surgery* ; Postoperative Complications/prevention & control* ; Coronary Occlusion/etiology*

AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

Objective:To explore the therapeutic effect and mechanism of Baicalin(BG)on chronic migraine(CM)rats.Methods:CM rat model was established by intermittent subcutaneous injection of nitroglycerin.Rats were randomly grouped into con-trol group,chronic migraine group(CM group),low-dose and high-dose Baicalin groups(BG-L group,BG-H group),Baicalin+MIP-1α recombinant protein group(BG+MIP-1α group)and CCR1 inhibitor ZK811752 group(CCR1-ZK group),with 10 rats in each group.General behavior of rats were observed and scored;von Frey fiber optic pain gauge was applied to measure the mechanical pain threshold of rats;Nissl staining was applied to observe the neuronal structure of ventrolateral periaqueductal gray(vlPAG);ELISA was applied to detect levels of TNF-α and IL-1β;immunohistochemical method was applied to detect expressions of pain related pro-teins c-Fos and CGRP;Western blot was applied to detect expressions of MIP-1α and CCR1 proteins.Results:Compared with Control group,the body mass,mechanical pain threshold,and the number of Nissl bodies in vlPAG area of rats in CM group were obviously reduced,the general behavioral score,levels of TNF-α,IL-1β,and expressions of c-Fos,CGRP,MIP-1α and CCR1 were obviously increased(P<0.05);compared with CM group,the body mass,mechanical pain threshold,the number of Nissl bodies in vlPAG area of rats in BG-L group,BG-H group and CCR1-ZK group were obviously increased,the general behavioral score,levels of TNF-α,IL-1β,and expressions of c-Fos,CGRP,MIP-1α and CCR1 were obviously reduced(P<0.05);compared with BG-H group,the body mass,mechanical pain threshold,and the number of Nissl bodies in vlPAG area of rats in BG+MIP-1α group were obviously reduced,general behavioral score,levels of TNF-α,IL-1β,and expressions of c-Fos,CGRP,MIP-1α and CCR1 were obviously increased(P<0.05).Conclusion:Baicalin has certain therapeutic effect on chronic migraine rats,and its mechanism may be related to inhibiting the activation of MIP-1α/CCR1 signaling pathway.

Objective:To identify the risk factors and their predictive value for complications in neonates with early-onset group B streptococcus (GBS) sepsis. Methods:This case-control study retrospectively analyzed 96 neonates with early-onset GBS sepsis (age of onset<7 days) admitted to Children's Hospital of Soochow University between January 1, 2007, and December 31, 2022. Patients were categorized into complication ( n=36) and non-complication ( n=60) groups. Receiver operating characteristic (ROC) curves determined optimal cutoff values of Pediatric Sequential Organ Failure Assessment (pSOFA) and Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2) for predicting complications in the neonates with early-onset GBS sepsis. Independent t-tests, Mann-Whitney U tests, Chi-square tests and Fishe exact tests were used for group comparison of general information, clinical manifestations, auxiliary examinations, and treatment during hospitalization. Multivariate logistic regression identified independent risk factors, and ROC curves evaluated their predictive performance for complications in the neonates with early-onset GBS sepsis. Results:ROC analysis identified pSOFA>4.5 scores and PELOD-2>5.5 scores as optimal thresholds for complication prediction in neonates with early-onset GBS sepsis. (1) The complication group exhibited higher rates of preterm birth [30.6% (11/36) vs. 5.0% (3/60), χ2=11.80], maternal clinical chorioamnionitis [25.0% (9/36) vs. 5.0% (3/60), χ2=6.50], prolonged rupture of membranes≥18 h [22.2% (8/36) vs. 5.0% (3/60), χ2=4.99], invasive mechanical ventilation [36.1% (13/36) vs. 13.3% (8/60), χ2=6.83], fever [22.2% (8/36) vs. 3.3% (2/60), χ2=6.70], lethargy [77.8% (28/36) vs. 51.7% (31/60), χ2=6.48], mottled skin as the initial clinical manifestation [38.9% (14/36) vs. 20.0% (12/60), χ2=4.07], leukopenia [44.4% (16/36) vs. 18.3% (11/60), χ2=7.59], hypoalbuminemia [27.8% (10/36) vs. 3.3% (2/60), χ2=10.16], pSOFA>4.5 [83.3% (30/36) vs. 35.0% (21/60), χ2=21.11], PELOD-2>5.5 [50.0% (18/36) vs. 5.0% (3/60), χ2=26.66], and dual-positive blood and cerebrospinal fluid cultures [25.0% (9/36) vs. 0.0% (0/60), Fisher exact test] compared to the non-complication group (all P<0.05). Serum creatinine [(88.4±17.7) vs. (61.9±17.7) μmol/L, t=－6.02], urea nitrogen [(3.7±0.4) vs. (3.4±0.6) mmol/L, t=－3.18], and lactate [(7.5±3.4) vs. (5.8±2.2) mmol/L, t=－2.80] were elevated, while fibrinogen [(2.2±1.1) vs. (2.7±1.0) g/L, t=2.03], pH (7.3±0.2 vs. 7.4±0.1, t=2.04), and albumin [(28.2±3.9) vs. (31.9±4.2) g/L, t=4.32] were reduced in the complication group (all P<0.05). (2) Multivariate analysis identified preterm birth ( OR=6.642, 95% CI: 1.210-36.473), along with hypoalbuminemia ( OR=8.202, 95% CI: 1.184-56.811), pSOFA>4.5 scores ( OR=5.284, 95% CI: 1.573-17.749), and PELOD-2>5.5 scores ( OR=8.464, 95% CI: 1.922-37.279) assessed on admission day 1 as independent risk factors (all P<0.05). The area under the curve for predicting complications in early-onset GBS sepsis neonates was 0.628 (95% CI: 0.523-0.724) for preterm birth, and 0.622 (95% CI: 0.517-0.719), 0.742 (95% CI: 0.642-0.826), and 0.725 (95% CI: 0.624-0.811) for hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores assessed on admission day 1, respectively. The combined predictive model integrating all four risk factors achieved the highest area under the curve of 0.868 (95% CI: 0.784-0.929). Conclusion:Preterm birth as well as hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores at admission are critical risk factors for complications in early-onset GBS sepsis, warranting heightened clinical vigilance.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective: To explore the efficacy of focal radiofrequency ablation (RFA) in the treatment of low-to-intermediate risk localized prostate cancer and its impact on postoperative urinary control and sexual function recovery，in order to explore the feasibility of minimally invasive methods for the treatment of localized prostate cancer. Methods: Clinical data of 28 patients with low-to-intermediate risk localized prostate cancer who underwent RFA in Nanjing Drum Tower Hospital，Affiliated Hospital of Medical School during Jun.2017 and Feb.2021 were retrospectively analyzed.The 5-year failure-free survival (FFS) rate，surgery related complications，postoperative urinary control and sexual function were collected.The differences between the survival curves of patients in the low-risk and intermediate-risk subgroups were assessed with log-rank test and Breslow test. Results: All surgeries were successfully completed under local anesthesia.During the median follow-up of 43 (40-49) months，the 5-year FFS rate predicted by Kaplan-Meier method was 78.57%; 25 patients (89.29%) did not experience surgery-related complications; 27 patients (96.43%) were able to control urination; 1 patient developed new-onset sexual dysfunction.There was no significant difference in the survival curves between patients in the low-risk and intermediate-risk groups (P>0.05). Conclusion: RFA for patients with low-to-intermediate risk localized prostate cancer has good clinical efficacy，little impact on urinary control and sexual function recovery，and few postoperative complications，which can be used as one of the treatment options for these patients.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.